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Mol Biol Cell. 2017 Jan 15;28(2):252-260. doi: 10.1091/mbc.E16-07-0541. Epub 2016 Nov 23.

Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity.

Author information

1
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143.
2
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158.
3
Cancer Research UK Beatson Institute, University of Glasgow, Glasgow G61 1BD, United Kingdom.
4
Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, United Kingdom.
5
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158.
6
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 joanne.engel@ucsf.edu.

Abstract

Pathogens can alter epithelial polarity by recruiting polarity proteins to the apical membrane, but how a change in protein localization is linked to polarity disruption is not clear. In this study, we used chemically induced dimerization to rapidly relocalize proteins from the cytosol to the apical surface. We demonstrate that forced apical localization of Par3, which is normally restricted to tight junctions, is sufficient to alter apical membrane identity through its interactions with phosphatidylinositol 3-kinase (PI3K) and the Rac1 guanine nucleotide exchange factor Tiam1. We further show that PI3K activity is required upstream of Rac1, and that simultaneously targeting PI3K and Tiam1 to the apical membrane has a synergistic effect on membrane remodeling. Thus, Par3 coordinates the action of PI3K and Tiam1 to define membrane identity, revealing a signaling mechanism that can be exploited by human mucosal pathogens.

PMID:
27881661
PMCID:
PMC5231894
DOI:
10.1091/mbc.E16-07-0541
[Indexed for MEDLINE]
Free PMC Article

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